Sepsis is an infection-induced syndrome driven primarily by dysregulated host inflammatory responses. This process induces complex physiological changes that provoke systemic inflammation and multi-organ dysfunction, severely threatening survival in advanced cases. N6-methyladenosine (m 6 A), the most prevalent eukaryotic RNA modification, orchestrates crucial regulatory functions across biological processes and is a focal point in epigenetics. This modification is dynamically controlled by three protein classes: writers that catalyze m 6 A deposition, erasers that mediate its removal, and readers that decode modification signals. Substantial evidence implicates m 6 A dysregulation in sepsis-induced multi-organ damage, encompassing cardiovascular dysfunction, acute lung injury, and acute kidney injury. This review synthesizes current mechanistic insights into m 6 A’s role in sepsis pathogenesis. By delineating how m 6 A governs inflammatory cascades and organ injury pathways, we evaluate its therapeutic targeting potential, providing translational frameworks for future research.